SYNONYM(S): hycamptamine; SKF 104864
COMMON TRADE NAME(S): Hycamtin® (multiple brands available)
Topotecan is a semi-synthetic analogue of camptothecin, an agent derived from the Oriental yew tree, Camptotheca accuminata. The cytotoxic effects of the camptothecins are believed to be related to their activity as inhibitors of topoisomerase – I, an enzyme involved in the replication and repair of nuclear DNA. As DNA is replicated in dividing cells, topoisomerase-I acts by binding to super-coiled DNA and causing single-stranded breaks in that DNA. As a result, topoisomerase –I is able to relieve the torsional stresses that are introduced into DNA ahead of the replication complex or moving replication fork. Topotecan binds to the DNA and the topoisomerase complex and prevents religation of DNA strand breaks, leading to cell death.
Topotecan is evenly distributed between blood cells and plasma. Pharmacokinetics are dose proportional.
|Cross blood brain barrier?||Yes|
Topotecan undergoes pH-dependent hydrolysis at pH of 4 or less to create an active lactone form, with the equilibrium favouring the ring-opened hydroxyacid form at physiologic pH. It is also metabolized in the liver to N-desmethyl topotecan.
|Active metabolites||Lactone form, n-desmethyl metabolite|
|Inactive metabolites||Hydroxyacid form, n-desmethyl metabolite, glucuronides|
Topotecan is eliminated primarily in the urine with some elimination via the biliary route.
|Urine||51% unchanged within 9 days, along with some metabolites|
|Half-life||(terminal) : 2-3 hours (IV)|
- For the treatment of metastatic cancer of the ovary after failure of initial or subsequent therapy
- For the treatment of sensitive (relapsed ≥ 60 days after first-line chemotherapy) small cell lung cancer after failure of first-line chemotherapy
- Cervical cancer
- Ewing's sarcoma
- Soft tissue sarcoma
Extravasation Potential: Minimal
|ORGAN SITE||SIDE EFFECT* (%)||ONSET**|
|Rash (16%) (may be severe)||I E|
|Gastrointestinal||Abdominal pain (22%)||E|
|GI obstruction (5%) (reported in ovarian cancer patients)||E|
|Nausea, vomiting (64%)||I|
|Hematological||Myelosuppression ± infection, bleeding (grade 4: 78%)||E|
|Hepatobiliary||↑ LFTs (8%) (2% severe)||E|
|Musculoskeletal||Muscle weakness (5%)||E|
|Musculoskeletal pain (5%)||E|
|Nervous System||Headache (18%)||E|
|Respiratory||Cough, dyspnea (22%)||I E|
|Pneumonitis (rare)||E D|
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.
Dose-limiting side effects are underlined.
** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)
The most common side effects for topotecan include nausea, vomiting, alopecia, diarrhea, constipation, fatigue, pain, abdominal pain, cough, dyspnea, anorexia and headache.
Prophylactic use of antiemetics was not routine in patients treated with topotecan.
Myelosuppression is the dose-limiting toxicity of topotecan, particularly neutropenia, which occurs more frequently and is often more severe than thrombocytopenia. It is dose-related, reversible and non-cumulative, but complicated by infection or fever in 23% of patients and 7% of cycles. Neutropenia is more severe in heavily pre-treated patients. Decreased renal function is associated with a lower MTD and more marked neutropenia. Neutropenic colitis (typhlitis/caecitis) have been reported in clinical trials.
For patients who present with cough, fever, dyspnea and/or hypoxia suggestive of interstitial lung disease (ILD), treatment should be interrupted and patients should be managed accordingly. If ILD is diagnosed, topotecan should be discontinued.
Most of the non-hematologic toxicities are mild to moderate in severity and not dose-limiting.
Refer to protocol by which patient is being treated. Numerous dosing schedules exist depending on disease, response and concomitant therapy; doses may be lower for combination regimens. Dosage may be reduced and/or delayed in patients with bone marrow depression due to cytotoxic/radiation therapy.
Prior to administration of the first course of topotecan, patients must have a baseline neutrophil count of ≥ 1.5 x 109/L, a platelet count of > 100 x 109/L, and a hemoglobin level of ≥90 g/L.
Dose levels: 1.5 mg/m2, 1.25 mg/m2, 1 mg/m2
Worst Toxicity Previous Cycle
Grade 4 neutropenia ≥ 7 days
Reduce dose by 1 dose level
Use G-CSF with next cycle
Cycle delay for hematologic toxicity
Platelets <25 x 109/L
Reduce dose by 1 dose level
Reduce dose by 1 dose level
Grade 3 GI or organ toxicity
Symptoms suggestive of pneumonitis
Hold and manage patient appropriately. Discontinue if confirmed.
Grade 4 GI or organ toxicity
|1. Do not retreat until neutrophils ≥ 1 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥90 g/L (after transfusion if necessary) and other toxicity ≤ grade 2.|
No dosage adjustment is required for treating patients with bilirubin < 171 μmol/L. Total topotecan clearance in patients with hepatic impairment only decreased by about 10%, as compared to the control group of patients.
|Creatinine Clearance (mL/min)||Adjusted dose|
No dosage adjustment needed other than for renal function as above.
Safety and efficacy have not been established.
- Mix in 50mL-100mL minibag (NS or D5W); infuse over 30 minutes.
- Final concentration should be between 0.02 mg/mL to 0.5 mg/mL.
- Patients with hypersensitivity to topotecan or any of its excipients
- Patients with pre-existing severe myelosuppression
- Patients with severe renal impairment (CrCl <20 mL/min)
- Use with caution in patients with risk factors for pneumonitis
Other Drug Properties:
Topotecan is not recommended for use in pregnancy. Adequate contraception should be used by both sexes during treatment, and for at least 6 months after the last dose.
Excretion into breast milk:
Breastfeeding is not recommended.
In vitro, topotecan did not inhibit CYP1A2, 2A6, 2C8/9, 2C19, 2D6, 2E, 3A or 4A.
|Cisplatin when given on day 1||↑ Severity of myelosuppression||Additive||Avoid or reduce doses of cisplatin and topotecan|
|G-CSF (concomitant)||Prolong duration of neutropenia||If G-CSF is to be used, it should not be initiated until day 6 of the course of therapy.|
|Curcumin (Tumeric)||May reduce effect of topotecan||Inhibits topotecan induced apoptosis||Avoid concomitant use|
|Phenytoin||↓ effect of topotecan||↑ clearance of Topotecan, due to possible ↑ in metabolism||Avoid or may need to increase topotecan dose|
|Docetaxel when given on day 4 of topotecan treatment||50% decrease in docetaxel clearance||Topotecan may change docetaxel metabolism by CYP3A4 inhibition||Give docetaxel on day 1 of topotecan treatment|
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
|Monitor Type||Monitor Frequency|
|Baseline and before each cycle|
Liver and renal function tests
|Baseline and at each visit|
Clinical toxicity assessment of GI, skin, infection, bleeding and pulmonary effects.
|At each visit|
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
New Drug Funding Program (NDFP Website )
- Topotecan - Single Agent Treatment of Platinum Sensitive Ovarian Fallopian Tube or Primary Peritoneal Cancer
- Topotecan - Platinum-Resistant Ovarian Fallopian Tube or Primary Peritoneal Cancer
Herben VM, Rosing H, ten Bokkel Huinink WW et al. Oral topotecan: bioavailability and effect of food co-administration. Br J Cancer 1999;80(9):1380-6.
McEvoy GK, editor. AHFS Drug Information 2011. Bethesda: American Society of Health-System Pharmacists, p. 1245-8.
Ormrod D, Spencer CM. Topotecan a review of its efficacy in small cell lung cancer. Drugs 1999;58 (3):533-51.
Product Monograph: Hycamtin® (topotecan). GlaxoSmithKline Inc., July 9, 2009.
Summary of Product Characteristics: Hycamtin® (topotecan). SmithKline Beecham (UK), October 28, 2010.
Somasundaram S, Edmund NA, Moore DT, et al. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res 2002;62(13):3868-75.
Zamboni WC, Gajjar AJ, Heideman RL, et al. Phenytoin alters the disposition of topotecan and N-desmethyl topotecan in a patient with medulloblastoma. Clin Cancer Res 1998;4(3):783-9.
November 2017 updated public funding (removed archived forms)
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